1. Field of the Invention
This invention relates to a synthetic peptide, to a synthetic vaccine comprising said peptide, to an agent for stimulation of antibody production to a naturally occurring antigen, and to a process for their preparation.
2. Discussion of Prior Art
Hepatitis B virus (HBV) vaccines have been prepared from lipoprotein particles containing hepatitis B surface antigen (HBsAg) isolated from plasma of chronic HBV carriers (McAuliffe et al., 1980). This source of antigen is costly and scarce, therefore research was initiated to produce the immunogen by recombinant DNA technology. Despite extensive efforts, the yield of immunogenic material has been disappointing (Burrell et al., 1979; Edman et al., 1981, Mackay et al., 1981). Only recently cloning the HBsAg gene led to production of lipoprotein particles of full immunogenic potency in S. cerevisiae (Valenzuela et al., 1982). However, for practical purposes, the yield of HBsAg particles was still very low. Therefore, several groups of workers have attempted to develop a synthetic hepatitis B vaccine searching by computer the amino acid sequence of HBsAg for continuous antigenic sites (Atassi, 1980), either indirectly by exclusion of hydrophobic sequences (Vyas et al., 1981; Lerner et al., 1981; Dreesman et al., 1982) or by direct search for hydrophilic structures (Hopp and Woods, 1981; Hopp, 1981; Prince et al., 1982).
It has been reported that when the DNA for the HBsAg gene is split into approximately two equal halves and cloned in E. coli, it produces two separate antigenic peptides (Mackay et al., 1981). This information has been confirmed by synthesis of antigenic (immunogenic) peptides derived both from the C-terminal (Lerner et al., 1981; Dreesman et al., 1982; Hopp and Woods, 1981; Hopp, 1981; Prince et al., 1982, Bhatnagar et al., 1982) and from the N-terminal (Lerner et al. 1981) halves of the HBsAg molecule. When the above synthetic peptides were mapped on a diagram of hydrophilicity of their amino acid residues, it was determined that practically all the peptides comprising the prominent hydrophilic domains in the sequence of HBsAg have already been synthesized (results not shown).